Could I inherit a rare genetic disorder?

Rare genetic disorders are, well...rare! Although the definition of a rare disease differs globally, any condition affecting less than 200,000 people is considered rare in the US.¹ Most people will never develop one. How likely you are to inherit one depends on the disorder, how it’s inherited, and a bit of genetic luck. And it turns out that some rare genetic disorders aren’t even inherited!

Typos in DNA: The Key to Rare Genetic Disorders

Think of your DNA as a giant instruction manual for building and running your body. Each gene is a sentence in that manual and sometimes a “typo” can change how the page is read. Some typos don’t do much, while others can affect how your body functions. When those typos cause noticeable effects that impact your health, scientists call that a genetic disorder. 

Some of these genetic disorders are extremely rare. For instance, Fabry disease affects 1 in 100,000 people while the prevalence of ALS worldwide is around 4.42 cases per 1,000,000 people.^2,3 Others are so unusual that there might just be a handful of known cases worldwide.

Mendel’s Rules: The Classic Genetics Playbook

Some genetic disorders follow simple rules of inheritance, called Mendelian inheritance. For example, Huntington’s disease is autosomal dominant, which means that the "typo" (which scientists refer to as a mutation) is in a gene on an autosome – that is, any chromosome that is not a sex chromosome (X or Y). In the case of Huntington’s disease, that mutation is on chromosome 4 and a single copy of the altered gene is enough to cause the disorder. If a parent carries it, each child has roughly a fifty percent chance of inheriting it.

On the other hand, autosomal recessive disorders like cystic fibrosis or Tay-Sachs disease require two copies of the disease-causing version of the gene, one from each parent, for a person to be affected. Parents who carry only one copy of the mutated gene are referred to as “carriers,” since they can pass the disease-causing gene to their kids but don’t have the condition themselves. That’s why disorders can sometimes skip generations!

Beyond autosomal conditions, there are also X-linked disorders which, like you might have guessed, are diseases where the gene responsible is located on the X chromosome. These types of conditions tend to mostly affect biological males since they only have one X chromosome. Duchenne muscular dystrophy is an example of an X-linked recessive disorder which affects about 1 in every 5,000 male infants.⁴ 

Even these seemingly straightforward patterns of inheritance can have surprises. Two people might have identical gene variants but only one of them might end up developing the disease! This is a phenomenon that scientists call incomplete penetrance. In other words, having the genetic variant for a particular disease doesn’t always mean you’ll end up developing that disorder.

When Genetics Gets Complicated

Most rare disorders, though, aren’t this simple. Many involve multiple genes and environmental factors. These are called polygenic disorders. That’s a fancy way of saying that dozens, hundreds, or even thousands of small changes in your DNA might each add a tiny risk, and things like nutrition, exposure to chemicals, or infections can influence whether a disorder shows up. 

For instance, congenital heart defects can result from a mix of several genetic variants combined with maternal health factors.⁵ Conditions like type 2 diabetes are similarly influenced by many genes along with environmental conditions.⁶ Scientists can’t predict these diseases as easily as Mendelian conditions — there’s just too many factors at play!

This is where genome-wide association studies (GWAS) come in. Scientists can now sequence the genomes of thousands of people with a particular condition and compare their genomes to a control group of people without the disease. This lets them identify gene variants that are found more commonly in the disease group and therefore could be contributing to the genetic risk of developing that condition. It’s important to note that these are just associations though — scientists need to do further validation to prove that a particular gene variant identified through GWAS is actually contributing to the disease.

Spontaneous Mutations: Nature’s Curveball 

Sometimes, though, disorders appear “out of the blue” — that is to say, they aren’t inherited from your mom or dad! These are caused by de novo mutations, which are new changes in DNA that happen in sperm, egg, or very early in development. This is why a child can have a rare disorder even if no one else in the family carries the disease-causing genetic variant. 

Why family history helps, but doesn’t tell the whole story 

Knowing your family’s medical history can be super helpful. It’s often the first clue doctors or genetic counselors use to understand your background. If a certain condition appears in several relatives, that might suggest there’s a hereditary component. Genetic counselors can map this out with a tool called a pedigree, which is a kind of family tree that tracks how disorders show up across generations.

But even with a detailed family tree, genetics rarely offers clear-cut predictions. Some people carry gene variants and never develop symptoms at all. Others may develop a disorder when no one else in their family has it. That’s why family history often only gives us clues rather than certainties. 

Still, the clues can guide testing options and next steps. Today, there’s a growing range of genetic testing methods that can help identify risks or confirm diagnoses: 

• Targeted genetic tests look for specific mutations known to cause a suspected condition. This kind of test is often used for patients who have a relative with a particular variant to determine if they have a familial condition. 
• Carrier screening checks if someone carries a recessive gene that could be passed on to children even if they don’t show symptoms themselves. 
• Whole genome sequencing (WGS) and whole exome sequencing (WES) go much broader, scanning thousands of genes—or even all of your DNA—to find rare variants that might explain unusual symptoms. 

For some families, these tests can bring clarity after years of uncertainty. For others, though, they can yield new questions: a genetic testing result might show a variant of uncertain significance (VUS), which means that scientists don’t yet know whether the change actually causes disease. Because of that, genetic results are best interpreted by professionals who understand both the science and the limits of current knowledge. 

So yes, rare diseases happen—but they’re the exception, not the rule. For those that live with them, each discovery offers hope and understanding. And every rare case can help scientists learn more about how our genes work!